The invention relates to assemblies for electrospray ion sources. Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions. It is especially advantageous for ionizing macromolecules due to its soft character without inducing too much fragmentation during ionization. The development of ESI for the analysis of biological macromolecules was rewarded with the Nobel Prize in Chemistry to John Bennett Fenn in 2002.
A liquid containing analyte(s) of interest is typically dispersed by electrospray into a fine aerosol from the tip of a capillary. Because ion formation involves extensive solvent evaporation, typical solvents for electrospray ionization are prepared by mixing water with volatile organic compounds, such as methanol or acetonitrile. To decrease the initial droplet size, compounds that increase conductivity, such as acetic acid can be added to the solution.
Large-flow electrosprays can further benefit from additional nebulization by an inert gas, such as nitrogen, which may emerge from an annular conduit opening proximate a tip of the capillary. The inert gas may also be heated in order to further promote evaporation of the spray mist. The solvent evaporates from a charged droplet until it becomes unstable upon reaching its Rayleigh limit. At this point, the droplet deforms and emits charged jets in a process known as Coulomb fission. During the fission, the droplet loses a small percentage of its mass along with a relatively large percentage of its charge. The aerosol, which as the case may be, encompasses gas-phase molecules, ions and tiny charged droplets, is sampled into the first vacuum stage of a mass spectrometer through an orifice (and/or subsequent transfer capillary) which can also be heated in order to finalize solvent evaporation from the remaining charged droplets and prevent any memory effects due to sample deposition on surfaces.
The ions observed by mass spectrometry may be quasi-molecular ions created by the addition of a proton and denoted [M+H]+, or of another cation such as sodium ion, [M+Na]+, or the removal of a proton, [M−H]−. Multiply charged ions such as [M+nH]n+ are often observed, which makes ESI particularly favorable for ionizing large macromolecules that would otherwise lie beyond usual detection ranges. For such macromolecules there can be many charge states, resulting in a characteristic charge state envelope.
Electrospray ionization has found favorable utility particularly for liquid chromatography-mass spectrometry (LC-MS, or alternatively high performance liquid chromatography-mass spectrometry HPLC-MS) which combines the physical separation capabilities of liquid chromatography (or HPLC) with the mass analysis capabilities of mass spectrometry. Generally, its application is oriented towards the detection and potential identification of chemicals in the presence of other chemicals, often in complex mixtures. Applications of LC-MS cover fields such as pharmacokinetics, proteomics/metabolomics, and drug development to name but a few.
As mentioned before, it has been known to use heated gas in order to promote evaporation of the droplets in the spray mist and thereby expedite the ionization process. The heated gas injected into and circulating in the ionization chamber may contact the liquid guiding capillary and transfer heat thereto. The temperature of the liquid in the capillary, however, should not exceed the boiling point since otherwise pressurized vapor within the liquid, upon emerging from the tip of the capillary, would disrupt the formation of small charged liquid droplets thereby deteriorating the ionization process and reducing ion yield. Certain analytes of interest such as proteins also respond with conformational changes to heat exposure (others even with degradation) which may be undesirable when the mass spectrometric analysis is coupled with an ion mobility analysis, for instance.
Therefore, attempts have been made to prevent excessive heat transfer to the liquid in the capillary. One way of dealing with this problem consisted in disposing a solid insulating sleeve or jacket made of fused silica about the capillary needle in order to maintain a certain temperature differential (U.S. Pat. No. 5,349,186 A to Ikonomou et al.). A similar approach in a slightly altered design was suggested by Thakur (U.S. Pat. No. 7,199,364 B2). But implementations according to such solutions result in a rather bulky design which counteracts an operator's general goal to minimize a spatial requirement for a capillary and conduit assembly.
Wittmer et al. (Anal. Chem. 1994, 66, 2348-2355) and Chen et al. (Int. J. Mass Spectrom. Ion Processes 1996, 154, 1-13) encountered problems with heat induced boiling of solvent in the capillary needle in an electrospray ion source with subsequent ion mobility drift cell which contained a heated drift gas. They suggested providing an active cooling mechanism having an outer conduit flushed with water as cooling medium which contacts a gas-filled conduit disposed about the capillary. A similar approach of active cooling was suggested by Mordehai et al. (US 2009/0250608 A1). Wu et al. (US 2010/0224695 A1), on the other hand, employ a heat exchanger which is in direct contact with the electrosprayer to control the temperature of the electrosprayer in another way of active cooling. However, the instrumental and procedural effort for maintaining active cooling, such as establishing circulation of cooling fluid, is significant.
In summary, a major problem with nebulizing ion sources utilizing a concentric nebulizer gas and a further concentric heated desolvation gas is the inadvertent heating of the central capillary. Unless the interaction length is short, the heat flux from the high temperature desolvation gas will raise the temperature of the nebulizer gas which in turn results in heating of the central capillary. Such heating may result in degradation of the sample or boiling of the solvent. Adding insulating material between the desolvation gas and nebulizer gas conduits, such as suggested by Thakur, can be effective but presents problems of finding a material with very stringent properties. It must have very low conductivity, be dimensionally stable, resist high temperatures and not outgas or shed particulates. Most materials fulfilling these requirements are bulky and their use would significantly increase the diameter of an electrospray assembly.
Hence, there is still a need for a simple and lean/compact way of preventing excessive heat transfer to the liquid in the capillary of an electrospray ion source.